Osteoarthritis (OA) is characterized by its degenerative effect on major extracellular matrix (ECM) components such as type II collagen and aggrecan in articular cartilage. This enhancement of articular cartilage ECM catabolism is largely mediated by the matrix metalloproteinase (MMP) family of collagenases and the ADAMTS family of aggrecanases. Furthermore, increase of the concentration of inflammatory cytokines such as IL-1β, which occurs during OA pathogenesis, often leads to repression of synthesis of type II collagen and aggrecan, and upregulation of MMP13 and ADAMTS-4 and -5, thereby favoring cartilage degeneration.
Matrilin-3 (MATN3) is a member of the non-collagenous matrilin family of ECM proteins that share common domains and similar functions. While MATN1 and MATN3 are distributed specifically in cartilage, MATN2 and MATN4 are distributed in many connective tissues. Mutation of MATN3 results in a variety of skeletal diseases including chondrodysplasia and osteoarthritis. MATN3 KO mice exhibit relatively normal skeletal development but develop accelerated articular cartilage degeneration during aging. However, the mechanism by which MATN3 acts chondroprotectively is yet unknown and traditionally it was believed that the role of MATN3 is purely structural as an ECM protein.